Sugar derivatives of compounds of the suprarenal cortical hormone series and process of making the same



Patented 20,

v 2,270,379-- UNITED STATES. PATENT OFFICE SUGAR DERTVATIVES OFCOMPOUNDS OF THE SUPRABENAL CORTICAL HOBMONE' gg ugs'un PROCESS OFMAKING THE Jersey No Drawing. Application February 20, 1939, Se-

rial No. 1938 .7 Claims.

This invention relates to the manufacture of A -21-oxy-pregnene-dione(3,20)

A 3,2 1 -dioxy-pregnene-one- A 1 1,21 -dioxy-pregnene-dione- (3,20) A-11-keto-21-oxy-pregnene-dione- (3,20) A -17,2l-dioxy-pregnene-dione-3,20)

A 1 1,17,21 -trioxy-pregnene-dione- (3,20) A-11-keto-17,21-dioxy-pregnene-dione-(3,20)

As saccharides there may be used for instance mono-, diortrisaccharides, such as glucoses, galactoses and galactose-glucoses.

The methods adopted in the invention may be such as is described forexample in Richter Anschiitz, Chemie der Kohlenstoiiverbindungen,

vol. 2, first half, page 359 (1935). This text-book describes forexample the action of hydrochloric acid on alcoholic sugar solutions,the reaction of alcohols with 1:2-oxides of sugars, and the manufactureof phenolglycosides from phenols and sugar acetates by zinc chloride orparatoluene sulfonic acid. But also other known catalysts furthering theetherification may be used, for example silver oxide, silver carbonate,mercury salts such as-mercury oxide, mercury acetate (cf. Berichte vol.62,'page 990 (1929)) and mercury succinate, emulsion and the glucosidaseof yeast.

The new compounds may have one or more saccharide residues in themolecule, and in addition hydroxyl groups which may be free oresterified or etherified. The saccharide residues may alternatively bepresent in the form of derivatives, for instance in the form of theiracylates. The new compounds are characterized by their good solubilityin water. They are useful in therapeutics.

The following examples illustrate the invention, the parts being byweight:

Example 1 A mixture of 1 part of A -21-oxy-pregnenedime-(3,20), 2 partsof acetobromoglucose and 2 parts of dry silver oxide are shaken togetherin l with dilute nitric acid and water.

257,545. In Switzerland February 23,

200 parts of absolute ether at room temperature for hours. The silveroxide mud separated by filtration is boiled for some time with freshether and the united ethereal solutions are washed From the stronglyconcentrated ethereal solution the tetracetyl-glucoside separates in theform of a white crystalline mass. It can be recrystallized from dilutealcohol F. 175-176 C.

For saponification the tetracetyl-glucoside is heated with 10 parts ofethanol and mixed with an alcoholic solution of sodium ethylate. Aftercarefully diluting with water and immediately neutralizing with diluteacetic acid, the product is evaporated to dryness. The residue isredissolved from little ethanol or methanol and the desired 4 -21-93glucosido) pregnene dione- (3,20) is obtained in the form of a whitepowder. The saponification may also be efiected with other hydrolizingagents, for example sodium hydroxide.

The same product is equally well obtained by starting from anotherderivative of glucose, for example pentacetyl-glucose.

In similar manner the glucosides of other compounds of the suprarenalcortical hormone series may be made. For example, starting from A -3,21dioxy pregnene one (20), A -11,21- dioxy pregnene dione -(3,20), A-17,21-dioxypregnene-dione- 3,20) A-11-keto-17,21-dioxypregnene-dione-(3,20), or A-11,17,21-trioxypregnene-dione-(3,20), there is obtained a correspondingderivative having two respectively three glucose residues in themolecule.

Other catalysts furthering etherification may be used for instance inorganic acids such as hydrochloric acid, para-toluene sulfonic acid,zinc chloride, mercury salts, such as mercury acetate, mercury oxide andmercury succinate, emulsin or the glucosidase of yeast.

As etherifying sugar derivatives there may be used in a quiteanalogousmanner, instead of mono-saccharide derivatives, alsoderivatives of diand trisaccharides, for example of galactose orgalactose-glucoses, and of other polysaccharides.

Example 2 1 part of A -21-oxypregnene-dione-(3,20), 2 parts ofacetobromolactose and 0.5 part of mercury acetate are mixed with partsof absolute benzene, and themixture is boiled for some time. The benzenesolution is worked up in the manner described in Example 1. Byevaporating the solvent the desired heptacetyl lactoside is ob- (Blactosido) -pregnene-dione 13,20) which is well soluble in water and maybe recrystallized from aqueous ethanol or methanol is obtained.-

By reaction of oxypregnene-dione withacetobromo-(G-gentiobiosido-d-glucose) there may be made by an analogousoperation the corresponding trisaccharide.

What we claim is:

1. A process for. the manufacture of new derivatives oi! compounds ofthe suprarenal cortical hormone series. comprising treating A-21-oxypregnene-dione-(320) with acetohromoglucose in contact withsilver oxide.

2. A process for the manufacture of new derivatives of compounds of thesuprarenal cortical hormone series, comprising treating A-21-oxypregnene-dione-'(3,20) with acetobromoglucose in contact withsilver oxide and then treating the product thus obtained withhydrolizing agents.

3. A process for the manufacture of new de-- ,4. The mono-saccharidederivative of A -2loXPDregnene-dione-(330).

5. The "p-glucoside 0t A -21-oxy-pregnenedione-(3,20) 6. The sugarderivatives of compounds selected from the group consisting of A-2i-oxy-pregnenedione -(3,20) A -3,2l-dioxy-pregnene-one-(20) A-11,21-dioxy pregnene dione (3,20) A l1- keto-21-oxy pregnenedione-(3,20) A-17,21- dioxy-pregnene-dione-(3,20) A--11,1'7,21-trioxy--pregnene-dione-(3,20); and A -11-keto-17,2l-dioxy-pregnene-dione-(3,20),and which are characterized by their solubility in water.

7. The monosaccharide derivatives of compounds selected from the groupconsisting of A -21-oxy-pregnene-dione-(3,20) A -3,21-dioxypregnene one(20) A -11,21-dioxy-pregnenedione-(3,20) A-11-keto-2l-oxy-pregnene-dione- (3,20) A -17,21-dioxy-pregnene-dione-(3,20) A11,1'l,2l-trioxy-pregnene-dione-(3,20); and A11-keto-17,2l-dioxy-pregnene-dione- (3,20) and which are characterizedby their solubility in water.

- KARL MIESCHER.

WERNER FISCHER.

